Synthesis of Pyrrole via a Silver-Catalyzed 1,3-Dipolar Cycloaddition/Oxidative Dehydrogenative Aromatization Tandem Reaction

Abstract

Pyrroles are an important group of heterocyclic compounds with a wide range of interesting properties, which have resulted in numerous applications in a variety of fields. Despite the importance of these compounds, there have been few reports in the literature pertaining to the synthesis of pyrroles from simple alkenes using a one-pot sequential 1,3-dipolar cycloaddition/aromatization reaction sequence. Herein, we report the development of a benzoyl peroxide-mediated oxidative dehydrogenative aromatization reaction for the construction of pyrroles. We subsequently developed a one-pot tandem reaction that combined this new method with a well-defined silver-catalyzed 1,3-dipolar cycloaddition reaction, thereby providing a practical method for the synthesis of multisubstituted pyrroles from easy available alkenes. The mechanism of this oxidative dehydrogenative aromatization reaction was also examined in detail.

Silver‐catalyzed pyrrole synthesis: An overview

“…Wang and coworkers put forward a novel method for the synthesis of multisubstituted pyrroles. [37] They carried out a one-pot methodology by combining Ag 2 CO 3 -catalyzed 1,3-dipolar cycloaddition reaction between imines 8 and alkenes 9 with benzoyl peroxide initiated oxidative dehydrogenative aromatization reaction to form pyrroles 10 via free radical mechanism (Scheme 3). Imines having various substituents on the phenyl ring reacted well and afforded good yields of the products irrespective of the electronic factors of the substituents.…”

Recent Advances for the Synthesis of N‐Unsubstituted Pyrroles

“…Wang's group developed a new method for synthesis of pyrroles 307 based on the benzoyl peroxide‐mediated oxidative dehydrogenative aromatization reaction [99] . They elaborated a one‐pot tandem reaction which combined this new method with a well‐known silver‐catalyzed 1,3‐dipolar cycloaddition reaction, thereby providing a practical method furnishing to multisubstituted pyrroles 307 from easy available alkene 306 a (Scheme 102).…”

One‐Pot Synthesis of Polysubstituted Pyrroles via Sequential Ketenimine Formation/Ag(I)‐Catalyzed Alkyne Cycloisomerisation Starting from Ylide Adducts

“…[ 6 ] In addition to classical Paal‐Knorr or Hantazsch reaction, [ 7 ] other new methods, including 1,3‐dipolar cycloaddition, C—H activations, multicomponent reactions, oxidative coupling cyclization reactions, and so on, have been reported. [ 8 ] For example, a general and practical method for the construction of pyrroles was proposed by a silver‐catalyzed cycloaddition of isocyanides with unactivated terminal alkynes. [ 9 ] Pagadala described an efficient catalyst‐free four‐component reaction of aromatic aldehyde, malononitrile, isocyanide and cyclic secondary amine to produce functionalized pyrroles with antitumor activity.…”